Quercetin potentiates insulin secretion and protects INS-1 pancreatic -cells against oxidative damage via the ERK1/2 pathway

Abstract

BACKGROUND AND PURPOSE Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic -cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting β-cells. Using the INS-1 -cell line, the effects of quercetin were determined on glucose- or glibenclamide-induced insulin secretion and on -cell dysfunctions induced by hydrogen peroxide (H 2O 2). These effects were analysed along with the activation of the extracellular signal-regulated kinase (ERK)1/2 pathway. N-acetyl-L-cysteine (NAC) and resveratrol, two antioxidants also known to exhibit some anti-diabetic properties, were used for comparison. EXPERIMENTAL APPROACH Insulin release was quantified by the homogeneous time resolved fluorescence method and ERK1/2 activation tested by Western blot experiments. Cell viability was estimated by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) colorimetric assay. KEY RESULTS Quercetin (20 μmol·L -1) potentiated both glucose (8.3 mmol·L -1)- and glibenclamide (0.01 μmol·L -1)-induced insulin secretion and ERK1/2 phosphorylation. The ERK1/2 (but not the protein kinase A) signalling pathway played a crucial role in the potentiation of glucose-induced insulin secretion by quercetin. In addition, quercetin (20 μmol·L -1), protected -cell function and viability against oxidative damage induced by 50 μmol·L -1 H 2O 2 and induced a major phosphorylation of ERK1/2. In the same conditions, resveratrol or NAC were ineffective. CONCLUSION AND IMPLICATIONS Quercetin potentiated glucose and glibenclamide-induced insulin secretion and protected β-cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing -cell dysfunction associated with diabetes deserves further investigation. © 2010 The British Pharmacological Society.